Islet Transplantation Using PKX-001
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|ClinicalTrials.gov Identifier: NCT03073577|
Recruitment Status : Recruiting
First Posted : March 8, 2017
Last Update Posted : October 13, 2022
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Islet Transplantation is a procedure used in people with difficult to control Type 1 Diabetes. Insulin producing cells (islets) are isolated from a deceased donor pancreas. After the cells are carefully isolated from the donor pancreas, the islets are transplanted into the recipient's liver. These transplanted islets may produce insulin.
One of the challenges with islet transplant is the death of some of the transplanted islets due to inflammation, oxidative stress and exposure to diabetogenic immunosuppressive agents associated with islet functional impairment and graft loss, especially linked to the use of calcineurin inhibitors, including tacrolimus (Tac).
Antiaging glycopeptide (PKX-001) is a small, stable, synthetic replica of antifreeze proteins (AFPs), which naturally occur in Arctic and Antarctic fish and have been shown protecting cells against harmful conditions. PKX-001 is a new drug that has been shown in lab studies to help islet cells survive isolation and keep them healthy and functioning. Most importantly, animal studies have shown that islets treated with PKX-001 were protected from the immunosuppressant (Tac) toxicity and retained their function in animals receiving islet transplant.
This study will involve up to 10 participants from the islet transplant waiting list at the Clinical Islet Transplant Program. All participants will receive islets treated with the medication PKX-001. PKX-001 will be used only in the islet preservation process, and will not be given to participants as medication.
The purpose of this study is to confirm the safety of transplantation of PKX-001 treated islets and to evaluate the cytoprotective capacity of PKX-001 in islet transplantation, especially its capacity to protect against Tac induced graft dysfunction.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Drug: Antiaging Glycopeptide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical Study Using Antiaging Glycopeptide (PKX-001) in Islet Transplantation|
|Actual Study Start Date :||February 17, 2017|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||September 2023|
Experimental: Treatment Group
PKX-001 will be supplemented to islet preservation CMRL-1066 medium at final concentration of 3 mg/mL during islet isolation process. On the day of transplantation, preserved islets supplemented with PKX-001 are collected and washed with Transplant Media, which does not contain PKX-001, as a standard procedure. The isolation team will evaluate the final islet product based on standard assays. Islets are maintained for minimal 6 hours up to 72 hours in supplemented CMRL1066-based media containing PKX-001 until the time of transplant. When product release minimal criteria are met, islets will be clinically transplanted into patients intraportally.
Drug: Antiaging Glycopeptide
Antiaging Glycopeptide (PKX-001) will be supplemented to islet preservation medium during islet isolation process. On the day of transplantation, preserved islets supplemented with PKX-001 are collected and washed with Transplant Media, which does not contain PKX-001, as a standard procedure. The isolation team will evaluate the final islet product based on standard assays used in standard of care practice. When product release minimal criteria are met, islets will be clinically transplanted into patients intraportally by percutaneous transhepatic access.
- Adverse event morbidity [ Time Frame: Up to 1 year post-transplant ]Adverse event morbidity within 1 year post-transplant
- Serious adverse event morbidity [ Time Frame: Up to 1 year post-transplant ]Adverse event morbidity within 1 year post-transplant
- Number of participants with insulin independence [ Time Frame: Day 90 post-transplant ]Number of participants who achieve insulin independence at Day 90 post-transplant
- Islet yield [ Time Frame: Day 0 ]Difference in islet yield between treatment group and current standard protocol data
- Engraftment index [ Time Frame: Day 90 post-transplant ]Difference in engraftment index between treatment group and current standard protocol data
- Islet viability [ Time Frame: Day 0 ]Difference in islet viability between treatment group and current standard protocol data
- Glucose stimulated insulin release [ Time Frame: Day 0 ]Difference in glucose stimulated insulin release between treatment group and current standard protocol data
- Oxygen consumption ratio [ Time Frame: Day 0 ]Difference in oxygen consumption ratio between treatment group and current standard protocol data
- Insulin requirement [ Time Frame: Day 0 ]Difference in insulin requirement between treatment group and current standard protocol data
- Beta-2 score [ Time Frame: Day 0 ]Difference in beta-2 score between treatment group and current standard protocol data
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|Ages Eligible for Study:||18 Years to 68 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
To be eligible the participant must have had type 1 diabetes mellitus (T1DM) for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:
- Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, a Clarke score ≥4, hypoglycemic (HYPO) score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI >400/>300.
Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and/or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
- Retrospective Control Inclusion Criteria:
All control participants will be included according to the immunosuppression / engraftment regimen used in this pilot, specifically the current standard of care islet transplant at the University of Alberta Hospital: Alemtuzumab/Basiliximab, Anakinra, Etanercept, Mycophenolate Mofetil and Tacrolimus.
- History of enrollment in any other islet transplant trials (at the discretion of the investigator).
- Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction <30%; or (c) evidence of ischemia on functional cardiac exam.
- Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
- Psychiatric disorder making the patient not a suitable candidate for transplantation (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
- History of non-adherence to prescribed regimens.
- Active infection including Hepatitis C, Hepatitis B, HIV, or Tuberculosis (TB) (subjects with a positive purified protein derivative (PPD) performed within one year of enrollment, and no history of adequate chemoprophylaxis).
- Any history of, or current malignancies except squamous or basal skin cancer.
- BMI > 35 kg/m2 at screening visit.
- Age less than 18 or greater than 68 years.
- Measured glomerular filtration rate (GFR) <60 mL/min/1.73 m2.
- Presence or history of macroalbuminuria (>300 mg/g creatinine).
- Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
- Baseline Hb < 105g/L (<10.5 g/dL) in women, or < 120 g/L (<12 g/dL) in men.
- Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial liver function test (LFT) panel with any values >1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
- Untreated proliferative retinopathy.
- Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast-feeding.
- Evidence of significant sensitization on panel reactive antibody (PRA) (at the discretion of the investigator).
- Insulin requirement >1.0 U/kg/day
- HbA1C >12%.
- Uncontrolled hyperlipidemia [fasting LDL cholesterol > 3.4 mmol/L (133 mg/dL), treated or untreated; and/or fasting triglycerides > 2.3 mmol/L (90 mg/dL)].
- Under treatment for a medical condition requiring chronic use of steroids.
- Use of coumadin or other anticoagulant therapy (except aspirin) or patient with prothrombin time (PT) / international normalized ratio (INR) > 1.5.
- Untreated Celiac disease.
- Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03073577
|Contact: Clinical Islet Transplant Program CITPfirstname.lastname@example.org|
|University of Alberta||Recruiting|
|Edmonton, Alberta, Canada, T6G2C8|
|Contact: Clinical Islet Transplant Program CITP 780-492-7942 email@example.com|
|Principal Investigator: James Shapiro, MD, PhD|
|Principal Investigator:||James Shapiro, MD, PhD||University of Alberta|
|Responsible Party:||University of Alberta|
|Other Study ID Numbers:||
|First Posted:||March 8, 2017 Key Record Dates|
|Last Update Posted:||October 13, 2022|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Type 1 Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Immune System Diseases